Many of the projects in this program project involve generating mutations in the germ line and somatic tissues of mice by performing homologous recombination, Cre/loxP recombination in ES cells and Cre/loxP recombination in vivo. These procedures for the manipulation of ES cells and the construction of mice are technically demanding and are most efficiently performed in a dedicated laboratory. The various alleles which the core will help to establish in the mouse germ line are described in detail in each of the individual projects. These alleles vary in complexity from "simple" knockouts to more sophisticated alterations generated through successive manipulations of ES cells. For example, in Project V, deletions of about 1Mb will be established on mouse Chromosome 16 using the chromosome engineering techniques pioneered in the laboratory/1. This particular technology requires two gene targeting steps and a Cre-loxP recombination step. Other examples of more sophisticated alleles include flanking the exons of some genes with loxP sites and targeting Cre to specific loci. All of these allele types have been generated previously by the laboratory and therefore this should not present any specific problems. A summary of the types of alleles which will be generated by the core is presented in Figure 1.